Prospective evaluation of the diagnostic efficacy of CA 19-9 assay as a marker for gastrointestinal cancers.

Levels of a new carbohydrate antigen, CA 19-9, which is a monosialoganglioside identified by a monoclonal antibody raised against colorectal carcinoma cells, were compared to conventional CEA assays in 615 sera from healthy controls, patients with benign gastrointestinal disorders, and patients with cancers of gastrointestinal or extragastrointestinal origin. Whereas CEA levels were higher in smokers, CA 19-9 values were independent of the smoking history. CA 19-9 was undetectable in lymphoma and myeloma patients, but some patients with extraintestinal epithelial cancers expressed this antigen in serum. For benign and malignant gastrointestinal diseases, CA 19-9 displayed higher sensitivity, specificity, and predictive values than CEA. CA 19-9 was elevated as frequently as CEA in patients with metastatic pancreatic cancer, but in patients with localized disease, CA 19-9 was elevated more often than was CEA. In colorectal cancer, patients with and without metastases were detected at similar rates by both assays. It is concluded that CA 19-9 is a marker of epithelial cancers, does not vary with the smoking status, and is superior to CEA in detecting gastrointestinal malignancies, especially those arising from the pancreatic gland.

Copper, zinc and copper/zinc ratio in chronic pancreatitis and pancreatic cancer.

Serum copper and zinc levels and their ratio were evaluated in 48 control subjects, 29 patients with pancreatic cancer, 46 with chronic pancreatitis and 32 with extra-pancreatic diseases, with the purpose of ascertaining modifications in chronic pancreatic disease. Hepatic involvement and age were also investigated as possible factors influencing results. Cu/Zn ratio was found to be significantly increased in pancreatic cancer (2.66 +/- 0.16, mean +/- SE) as compared to controls (1.39 +/- 0.06, p less than 0.001), chronic pancreatitis (1.82 +/- 0.09. p less than 0.001) and extra-pancreatic diseases (1.81 +/- 0.18, p less than 0.001), but without practical clinical value. Serum zinc levels appear to decrease with age, while copper and Cu/Zn ratio increase. However, covariance analysis demonstrated that age does not play an important role in influencing copper and Cu/Zn ratio. A decreased liver synthetic function, at least in part age-related, seems to be an additional factor in decreasing serum zinc values.

Is maximal acid output useful in identifying relapsing duodenal ulcer patients?

In a group of 94 duodenal ulcer patients consecutively studied and followed-up for 1 year, subjects with maximal acid output (M.A.O.) above 60 mmol/hour (mostly heavy-smoking men), were found to relapse more frequently than those with lower M.A.O. values (72.2% versus 27.6%; p less than 0.0005). A significantly higher relapse rate was also detected in patients treated with maintenance dosages of effective antisecretory drugs (cimetidine, ranitidine, pirenzepine) and presenting M.A.O. over 60 mmol/hour. It is yet to be established whether an alternative therapeutic regime may prove effective in preventing ulcer recurrence in patients with gastric hypersecretion.

CEA and ferritin in chronic pancreatic disease: a comparative evaluation.

CEA and ferritin were determined in 90 subjects with the aim of comparing their value in the diagnosis of pancreatic malignancy. Ferritin was shown to be more sensitive than CEA in detecting pancreatic cancer patients (68.4% and 57.9%, respectively) all of whom were, however, in an inoperable stage. In contrast, CEA showed a higher specificity as compared to ferritin (77.4% and 47.2%, respectively), the latter being frequently increased in inflammatory conditions such as chronic pancreatitis. The simultaneous assessment of CEA and ferritin showed the highest sensitivity when either parameter was found to be pathological and the highest specificity when both were. The receiver-operating characteristic curves demonstrated that CEA is more discriminating than ferritin for all serum values. Neither ferritin nor CEA may be considered a practically suitable marker of pancreatic cancer.

CA 19-9 in the differential diagnosis between pancreatic cancer and chronic pancreatitis.

CA 19-9 serum concentration was determined by a immunoradiometric technique in 130 subjects to evaluate its role in differentiating pancreatic cancer from chronic pancreatitis. Two threshold values were chosen, 17 and 37 U/ml. With the former, sensitivity, specificity and diagnostic accuracy were 86.7, 62.3 and 49.0 respectively, with the latter 73.3, 87.0 and 60.3%. The receiver-operating characteristic curves demonstrated a satisfactory discriminating capacity of CA 19-9 as regards pancreatic cancer and chronic pancreatitis; in contrast, the discrimination was poor for other gastrointestinal diseases, mainly of a malignant nature.

A kinetic assay for human urinary kallikrein determination.

A simple kinetic method for human urinary kallikrein determination is proposed. In this assay, the release of p-nitroaniline from the chromogenic substrate S-2266 at 37 degrees C and pH 8.2 is followed spectrophotometrically at 405 nm. The delta A/5 min (0-5 min) interval was chosen. This assay was shown to have good sensitivity since enzyme concentrations as low as 0.00125 KU/ml could be measured. The use of dialyzed urines minimizes the interferences associated with high urinary salt concentration. Because of its precision and reproducibility, this kinetic assay may be proposed in clinical investigation.

Recurrence of duodenal ulcer under continuous antisecretory treatment: an approach to the detection of predictive markers.

Seventy consecutive duodenal ulcer patients endoscopically followed up and treated after ulcer scarring with maintenance dosages of effective antisecretory drugs for 1 year were studied in order to identify the factors associated with ulcer relapse. Logrank test, discriminant analysis (Rao's method), and chi 2 were used in evaluating the results. Nineteen patients (27.1%) relapsed. Duodenal ulcer was found to relapse more frequently in patients with total serum pepsinogen more than 109 micrograms tyr X ml-1 X 24 h-1 and in patients with maximal acid output more than 60 mmol/h (Logrank test; both p less than 0.025). Discriminant analysis showed that blood group, age at onset of the disease, and sex were together useful in recognizing subjects relapsing within 6 months' maintenance treatment (77.1% cases correctly classified); age at onset of the disease, alcohol intake, and smoking habit were together useful in picking out subjects relapsing throughout the entire observation period (1 year) (61.76% cases correctly classified). Our data suggest that: 1) duodenal ulcer subjects with elevated serum pepsinogen or maximal acid output are significantly more prone to relapse than patients with normal or slightly increased values; 2) genetic and acquired factors (such as blood group A, early onset of the disease, male sex, alcohol intake, and cigarette consumption) may have a role in influencing ulcer relapse.

Study of retinol-binding protein in pancreatic cancer.

Serum RBP, prealbumin, and zinc were evaluated in normal subjects and patients with pancreatic cancer and chronic pancreatitis. A significant decrease of RPB was found in pancreatic cancer patients compared with controls. A concomitant reduction of prealbumin and zinc was also observed. Multiple regression analysis suggested that the modification of RBP serum levels might be accounted for mainly by diminished prealbumin levels, while the direct role of zinc is negligible.

Combined evaluation of serum ribonuclease and ferritin: any advantages in pancreatic cancer diagnosis?

In 116 subjects, serum ribonuclease (RNase) and ferritin were determined in order to evaluate whether their combined evaluation might improve the diagnostic accuracy of each test. Significantly higher levels were found in pancreatic cancer patients both for RNase and ferritin than in control subjects and chronic pancreatitis. Sensitivity and specificity in diagnosing pancreatic cancer were 86% and 46%, respectively for RNase; 76% and 65% for ferritin. One of the two tests was pathological in 100% of pancreatic cancer, with a specificity of 29.9%; both were pathological in 62.1%, with a specificity of 82.1%. The results emphasize the limits of the combined assessment of pancreatic cancer markers.

Personality and psychological factors in chronic duodenal ulcer. Their interaction with biological parameters.

Forty patients with chronic duodenal ulcer were studied to determine whether some particular personality and psychological factors are associated with this disease. To this purpose the Cattell's PF 16 personality Test was utilized. Duodenal ulcer population presented a typical personality profile characterized by: high anxiety, dependence and introversion. Some biological parameters, suggested as predictors of slow healing and/or relapse of ulcer, were studied: patients with maximal acid output greater than 60 mEq/h and /or total serum pepsinogen greater than 109 micrograms tyr/ml/24 hrs and/or serum pepsinogen group I greater than 99 ng/ml showed an anxiety level significantly higher than that of patients with values less than the reported thresholds. These results suggest a contributory role by psychological factors in duodenal ulcer disease. The association of anxiolitic drugs to the traditional antiulcer therapy may be proposed, particularly in hypersecretors.

Carcinoembryonic antigen in gastric juice collected during endoscopy. Value in detecting high-risk patients and gastric cancer.

In order to ascertain the role of gastric carcinoembryonic antigen (CEA) determination in detecting patients with a risk for gastric cancer, 69 subjects were studied; 23 were referred for endoscopy because of dyspepsia but without obvious macroscopic lesions, 27 with duodenal ulcer, 11 with benign gastric ulcer, 8 with gastric cancer. The following results were obtained by subdividing the material according to the histologic interpretation of the results of gastric mucosal biopsies: (1) in the presence of minor histologic abnormalities of the gastric mucosa, CEA in gastric juice was under 100 ng/ml in all but five cases; and (2) in moderate or severe chronic atrophic gastritis (associated or otherwise with intestinal metaplasia or dysplasia), and in gastric cancer, gastric CEA ranged between 224 and 3120 ng/ml in all but two cases. Although not diagnostic for gastric cancer, gastric CEA is a promising test in detecting patients at risk, including those with dysplasia of the gastric mucosa.

Actual role of pepsinogen group I in the study of upper gastrointestinal diseases.

The role of serum PG I in screening patients with chronic atrophic gastritis and gastric cancer, and in detecting peptic ulcer patients with high relapse risk, was ascertained in 276 subjects. Although not diagnostic per se, PG I was found to be under 20 micrograms/L in patients with chronic atrophic gastritis and in some gastric cancer or partially gastrectomized patients. In patients presenting with relapsing duodenal ulcer, PG I values were significantly higher than in the non-relapsing ones, but a satisfactory identification of all the duodenal ulcer patients with high relapse risk was not possible on this basis. Even the correlation between PG I and MAO was not accurate in every subject considered. These results suggest that the value of PG I is limited to assessing patients with upper gastrointestinal diseases in which a reduction of peptic secretion, and therefore of PG I in serum, is present.

Risk of hepatitis B virus infection following upper gastrointestinal endoscopy: a prospective study in an endemic area.

A prospective survey, comprising 623 consecutive upper gastrointestinal endoscopies (in 588 patients) was carried out simultaneously at two endoscopy centres of a Mediterranean country, without altering the routine procedures. Each patient was tested for HBsAg, and sera found to be HBsAg-positive were tested for HBeAg/antiHBe: 40/588 (7.1%) subjects were found to be HBsAg-positive and 6 of them were HBeAg-positive. Sera of the first 5 HBsAg-negative patients in whom the same endoscope and/or biopsy forceps were used after a HBsAg-positive subject, were tested for antiHBc to ascertain antecedent HBV immunity: 77/136 (56.6%) were found to be antiHBc-positive. Forty-eight out of the 59 individuals "at risk" lacking evidence of previous HBV infection were contacted 6 months after endoscopy: none reported symptoms of hepatitis; 40 of them had blood tests for HBsAg and antiHBc: none showed serum markers of HBV infection. It is therefore concluded that, in spite of the high number of HBsAg carriers among endoscopy candidates, the risk of HBV spread during upper G.I. endoscopy is very low, even in high prevalence areas.

Urinary ribonuclease excretion in pancreatic disease.

Urinary ribonuclease output and indices of renal tubular integrity were evaluated in control subjects and patients with pancreatic cancer, chronic pancreatitis and extrapancreatic diseases. The aim of the study was to ascertain the contribution to such diagnoses of ribonuclease determination in urine, and the possible influence of tubular damage on the extent of ribonuclease excretion. Information from the ribonuclease assay in urine offered no advantage over that obtained by the same determination in serum; tubular damage may contribution in some cases to an elevated ribonuclease excretion.

Gastric epithelial dysplasia and sulphomucin-type intestinal metaplasia.

The HID-AB histologic staining technique, which distinguishes sulphomucin from sialomucin types of intestinal metaplasia, was employed in endoscopic gastric mucosal biopsies to evaluate their frequency of association with epithelial dysplasia. Sulphomucin-type intestinal metaplasia was found in 33% of the cases under observation; moderate or severe dysplasia was only associated with this type of intestinal metaplasia. Its precancerous significance can be ascertained only by means of prospective studies.

Is mild gastric epithelial dysplasia an indication for follow-up?

We evaluated the changes over 1-55 months in mild gastric epithelial dysplasia (a relatively frequent, but not widely studied histological lesion) in 20 patients (11 with benign gastric ulcer, eight with chronic gastritis, and one after Billroth 2 operation), in order to ascertain whether to follow-up such patients in the future. Regression of the lesion was documented in 13 (65%), and no change in six (30%). Progression from mild to moderate dysplasia occurred in only one patient (5%). As mild dysplasia regresses or remains unchanged in most patients, at least over the short-term, specific follow-up is probably unnecessary. Nevertheless, a rational program of monitoring the associated precancerous conditions is in order.